tbuckley/cabot-search huggingface dataset:
Utility of circulating tumor DNA as a tool to detect minimal residual disease in patients with metastatic cancer and durable response following treatment with immune checkpoint inhibitors.
Authors: Muhammad Zubair Afzal, Flanklin E. Corea-Dilbert, Bret Wankel, John P. Palmer, Jonathan P. Pirruccello, Soham Kale, Aditya Sharma, Ziyao Lu, Samer Ibrahim, Yuanzhen Cao, Tayyaba Sarwar, Keisuke Shirai
Journal: Journal of Clinical Oncology (2023)

e21563 Background: Circulating tumor DNA (ctDNA) is tumor-derived fragment of DNA circulating in plasma. ctDNA has been used to detect minimal residual disease (MRD) in early-stage cancers after curative intent therapy. However, ctDNA based MRD concept is not investigated in metastatic disease. There is a lack of clarity around optimal timing to stop immune checkpoint inhibitors (ICI) in melanoma and lung cancer patients who have achieved durable response (DR) and MRD may have a role here to select right patients to stop therapy at an optimal time. Methods: This is prospective study on metastatic lung cancer and melanoma patients with DR treated with ICI. DR is identified as objective response (CR/PR) by modified WHO criteria lasting ≥6 months continuously. We utilized Signatera assay by Natera. Signatera uses tissue from original biopsy of the patients and develop multiplex PCR based personalized assay to detect MRD. The level of ctDNA is reported in mean tumor molecules per mL. We obtained ctDNA assay at baseline, month 3 and month 6 at their routine follow up visits. If applicable, ctDNA assay was done at the time of progression, and 3 months after resuming treatment. Results: We identified 29 melanoma and 17 Lung cancer (both small cell and non-small cell) patients with metastases and DR. Median age was 69 years in both cohorts. Median duration of ICI was 14 months in melanoma and 24 months in lung cancer cohort. ctDNA assay was obtained in 26 melanoma and 13 lung cancer patients. One small cell lung cancer patient had detectable ctDNA at baseline, although radiographically, the patient had DR. The rest of the patients in both cohorts had undetectable ctDNA. 2 melanoma patients developed detectable ctDNA on subsequent assays and their therapies were changed. One small cell lung cancer patient has persistently detectable ctDNA on subsequent assays but remained in DR. A total of 10 patients in both cohorts decided to stop their therapy following several -ve ctDNA assay. Conclusions: The role of ctDNA needs to be investigated in advanced/metastatic settings as MRD may have a role to identify patients who may benefit from treatment break. MRD surveillance may also support radiographic assessment. [Table: see text]
Efficacy and safety study with alectinib in advanced ALK-positive non-small-cell lung cancer.
Authors: Laura Fernández Madrigal, Victoria García Samblás, María Amor Urbano, Angel Inoriza
Journal: Journal of Clinical Oncology (2023)

e21153 Background: 5% of patients with non-small-cell lung cancer (NSCLC) have a translocation of the ALK (anaplastic lymphoma kinase) gene on chromosome 2. The phase III clinical trial (ALEX study) analyzed the efficacy and safety in patients with a diagnosis of NSCLC and ALK mutation -positive (ALK+) randomized to alectinib versus crizotinib. The objective of our study is to describe our results with alectinib. Methods: Observational and descriptive study of patients with advanced NSCLC and ALK+ treated with alectinib in the period 2019-2022. Sociodemographic and clinical variables, toxicity profile, objective response rate (ORR), treatment response and progression free survival (PFS) were extracted and entered into IBM SPSS Statistics 22 for statistical analysis. Results: 7 patients received treatment. The median age was 46 years. Baseline characteristics: male (57%); non- Asian race (100%); non-smoker (57%), ECOG 0-1 (100%). All had adenocarcinoma histology. 57% had liver metastasis and 37% central nervous system metastasis at the time of diagnosis. The most frequent symptom was dyspnea (43%). Only one patient was previously terated with 2 lines of chemotherapy and a 3rd line with crizotinib prior to alectinib. Adjuvant chemotherapy was administered in one patient. The rest of the participants received alectinib as first line. The most frequent toxicities were: grade 1-2 increased alanine and aspartate aminotransferase (70%); grade 1 anemia (28.6%); grade 1 increased blood bilirubin (28.6%), skin toxicities (71.5%), myalgia (57%), visual disorders (28.6%); constipation (28.6%) and sinus bradycardia (14.5%). A 28.6% incidence of dose reductions due to adverse events (AEs) with alectinib. One patient had to discontinue treatment with alectinib due to grade 4 AEs consisting of toxic pneumonitis.Hospital admission was required. The ORR was 57.2%. Complete response ocurred in 28.6% of patients. The median response to treatment was 16 months and the median PFS was 16 months. Conclusions: The sociodemographic characteristics of our patients were similar to those described in the ALEX trial. However, the AEs were higher in our study. The ORR was lower in our study, despite obtaining a high percentage of complete responses. We have a reduced number of patients who have been treated with alectinib to obtain final conclusions efficacy.
Measuring variation in the quality of systemic anti-cancer therapy delivery across hospitals: A national population-based evaluation.
Authors: Jemma Megan Boyle, Jan van der Meulen, Angela Kuryba, Thomas E Cowling, Christopher M. Booth, Nicola S Fearnhead, Michael Braun, Kate Walker, Ajay Kumar Aggarwal
Journal: Journal of Clinical Oncology (2023)

6593 Background: To date, there has been little systematic assessment of the quality of care associated with systemic anti-cancer therapy (SACT) delivery across national healthcare systems. We evaluated hospital-level toxicity rates during SACT treatment as a means of identifying variation in care quality. Methods: All colorectal cancer patients receiving SACT within 106 English National Health Service hospitals between 2016 and 2019 were included. Severe acute toxicity rates were derived from hospital administrative data using a validated coding framework. Variation in hospital-level toxicity rates was assessed separately in the adjuvant and metastatic settings. Toxicity rates were adjusted for age, sex, comorbidity, performance status, tumour site, and TNM staging. Results: Of the 8,173 patients receiving SACT in the adjuvant setting, 2,074 (25%) had a toxicity with adjusted hospital-level rates varying from 11% to 49%. Of the 7,683 patients receiving SACT in the metastatic setting, 3,625 (47%) had a toxicity with adjusted hospital-level rates varying from 25% to 67%. Compared to the national mean toxicity rate in the adjuvant cohort, six hospitals were more than 2 standard deviations (2SD) above, and four hospitals were more than 2SD below. Similarly, in the metastatic cohort, six hospitals were more than 2SD above, and seven hospitals were more than 2SD below the national mean toxicity rate. Conclusions: There is substantial variation in hospital-level severe acute toxicity rates in both the adjuvant and metastatic settings, despite comprehensive risk-adjustment. Ongoing reporting of this performance indicator can be used to focus further investigation of toxicity rates and stimulate quality improvement initiatives to enhance care.
Trends in presentation, treatment, and survival in young multiple myeloma patients age 50 and under from 2000-2021.
Authors: Anupama Deepa Kumar, Michelle Alyssa Quan, Caitlin Costello, Rosenberg Aaron
Journal: Journal of Clinical Oncology (2023)

e20028 Background: Multiple myeloma (MM) is a disease predominantly of older adults with an average age of 69 at diagnosis. Limited data is available on the diagnostic details and outcomes of MM patients ≤50 years old, and particularly how these trends have changed over the past two decades. We present data from one of the largest retrospective cohorts of younger MM patients. Methods: This retrospective review identified 213 MM patients by pooling two datasets: 88 MM patients aged ≤50 years at first stem cell transplant (SCT) between 1/1/2000-6/1/2021 at University of California (UC), San Diego; and 125 MM patients age ≤50 years old at diagnosis between 1/1/2014-7/1/2021 at UC Davis. Demographics, diagnostic details, treatment, response, and overall survival (OS) data were collected. Results: The pooled dataset included 209 patients with MM and 4 with plasma cell leukemia. The median age was 45, with 58 (27%) Hispanic and 37 (17%) Black patients. In 89 patients with available data, 23% were R-ISS-1, 58% were R-ISS-2, and 19% were R-ISS 3. Overall, 14% of patients had high-risk cytogenetics [ t(4;14), del17p, or t(14;16]] . Patients diagnosed and treated in 2000-2010 were more likely to have received doublet or cytotoxic chemotherapy for induction therapy, while 80% of patients in 2010-2021 received triplet-based therapies. Responses to induction improved across decades, with 23% of patients in the earlier cohort vs 49% patients in the later cohort achieving a very good partial response (VGPR) or better. Eighty-five percent of patients received a SCT, the majority being autologous with only 13 upfront or salvage allogeneic SCTs in the earlier and 1 in the later cohort. The median OS for the entire cohort is 168 months, 171 months in the early cohort, and not reached in 2011-2021 cohort. Conclusions: We present retrospective data of a large and diverse cohort of California MM patients ≤50 years old, with nearly 50% of patients from underrepresented populations spanning over 2 decades. We found similar diagnostic features and risk group to those reported in the general MM population. Noticeable improvements in treatment responses were seen in the later decade with the introduction of modern therapies. A median OS of 14 years for the entire cohort over 20 years offers a glimpse into the hopeful promise for extended survival of younger patients as more effective therapies lead to deeper and more durable responses. [Table: see text]
National Coalition for Cancer Survivorship State of Survivorship Survey.
Authors: Shelley Fuld Nasso, Ana Maria Lopez, Veronika Panagiotou
Journal: Journal of Clinical Oncology (2023)

e18684 Background: The National Coalition for Cancer Survivorship (NCCS) conducts an annual State of Survivorship Survey to delve into the cancer survivor journey. The survey is needed to identify health disparities, gaps in quality care and assessment of the health care landscape that needs policy change at the national level. The survey objective is to better understand the differences in cancer survivor attitudes, experiences, and needs at every stage of the cancer journey. The survey identifies who the under-served audiences in the cancer community are, what are their specific challenges, and how the system can better meet their needs. Methods: Phase one was 15 virtual interviews of young adults; Hispanic adults; men. Phase two was a nationwide survey of 2,078 patients and survivors. Surveys were recruited through an online non-probability sample with quotas set to ensure demographically representative audiences. Phase three was a survey invitation to all NCCS email contacts, patient advocacy organizations, followers on social media to take the survey. The NCCS connected group was 670 patients and survivors. Results: We segmented the patients into experiential categories: those who have had positive experiences during their journey, mixed, and negative. Nearly three-quarters of respondents reported they were very satisfied with their treatment and care, due to a high degree of trust in and the relationship with their health care team. However, large disparities exist for those in the Negative Experience group. 68% of respondents overall said they always felt their health care provider listened to and respected their concerns, while only 47% of Hispanic respondents and 47% of individuals with metastatic cancer agreed. Similarly, 68% overall said they could always talk to their health care provider about their concerns, while 46% of Hispanic respondents and 50% of individuals with metastatic cancer agreed. Further, levels of trust were high, but groups with lower levels of trust included young adults, Blacks, Hispanics, people living with metastatic cancer. The Negative Experience group gave providers lower satisfaction scores and used terms like “bullied,” “ignored,” “test subject,” and “rushed” to describe their care. While majorities of patients said their health care team was a critical support network during treatment, followed by family/friends and faith, the Negative Experience and Mixed Experience audiences were significantly less likely to report support in any areas of their life during treatment. Conclusions: The survey is sharing the lived experience of cancer care today and brings to light the health disparities. The results show that part of this disconnect is demographic — people of color, younger, and lower socioeconomic status patients are more likely to be in the Mixed and Negative Experience segments. And part of it is experiential — these patients struggle through the their treatment and care.
Older patients with early-stage triple-negative breast cancer: The Memorial Sloan Kettering Cancer Center experience.
Authors: Iris Zhi, Diana E Lake, Fiona Ehrich, Yuan Chen, Beatriz Korc-Grodzicki, Larry Norton, Mark E. Robson, Jasmeet Chadha Singh
Journal: Journal of Clinical Oncology (2023)

12063 Background: Approximately 15% of cases of early-stage triple-negative breast cancer (TNBC) are diagnosed in individuals over the age of 70. Despite studies indicating that older patients derive similar benefits from polychemotherapy as younger patients, breast cancer specific mortality among older patients remains disproportionately high. Use of the comprehensive geriatric assessment (CGA) and individualized risk tools can help tailor treatment and minimize negative side effects while preserving quality of life. We performed a retrospective analysis of patients ≥ 70 years of age diagnosed with stage I-III TNBC at Memorial Sloan Kettering Cancer Center between 2015 and 2019 to describe clinical practices for managing this population. Methods: Demographics, CGA, systemic therapy data were collected from electronic medical records. A multivariable logistic regression model was used to identify factors that were independently associated with the probability of receiving chemotherapy. Results: We included 159 women, with a median age of 74.5 years (range 70-96). 67 (42%) had stage I disease, 71 (45%) had stage II, and 21 (13%) had stage III. 29 (18%) reported difficulty in Activities of Daily Living (ADL), 34 (21%) reported difficulties in Instrumental Activities of Daily Living (iADL), and 40 (26%) were identified as having a high risk for falls. 25 (17%) patients underwent CGA per physician’s choice. The prevalence of cardiac risk factors was as follows: hypertension in 80 patients (50%), diabetes in 25 (16%), obesity in 7 (4.4%), heart failure in 1 (0.6%). 147 underwent breast surgery, with 106 (67%) receiving lumpectomy and 41 (26%) mastectomy. 97 (61%) patients received chemotherapy: 35 (22%) neoadjuvant and 62 (40%) adjuvant. Anthracycline, Cyclophosphamide, Paclitaxel (AC-T) and Cyclophosphamide, Methotrexate, Fluorouracil (CMF) were the most common regimens. In multivariable logistic regression analysis, use of chemotherapy was associated with younger age (odds ratio [OR] 0.84 for one year increase in age, 95% confidence interval [CI] 0.75-0.93, p = 0.001) and higher disease stage (stage II vs. I OR 4.97, 95% CI 1.66-16.4, p = 0.006; stage III vs. I OR 22.0, 95% CI 3.3-312, p = 0.006). No significant difference was found in geriatric referrals, cardiovascular risk factors, or difficulties with ADL or iADL between those receiving or not receiving chemotherapy. Conclusions: In our single center experience, 61% of older patients with early-stage TNBC received chemotherapy, with AC-T and CMF being the most common regimens. The referral rate for CGA was low. Age &lt; 75 years and higher disease stage were significantly associated with receiving chemotherapy. Overcoming barriers to incorporating CGA and toxicity prediction into routine clinical practice is crucial for personalized treatment in this population.
Morbidity of single-fraction spine radiosurgery for metastatic disease.
Authors: Ulysses Grant Gardner, Shearwood McClelland
Journal: Journal of Clinical Oncology (2023)

e24116 Background: The optimal management of metastatic spine disease involves radiation therapy, with stereotactic radiosurgery (SRS) utilization having increased in adoption while proving to be efficacious and safe. Spine SRS morbidity (fatigue, dermatitis, nausea and esophagitis) is generally mild and depends on the spinal vertebral level(s) treated. More severe adverse events such as vertebral compression fracture (VCF), radiation-induced myelopathy, and tracheoesophageal (TE) fistula have been documented. The potential benefits of single-fraction SRS (sfSRS) over multi-fraction SRS include increased patient convenience, decreased financial toxicity, and increased treatment completion rates. These benefits may potentially be overshadowed by the morbidity of sfSRS versus multifraction SRS. In this analysis, we perform the first comprehensive examination of sfSRS morbidity in the treatment of spinal lesions. Methods: An extensive search of the PubMed database was undertaken through 2/2/23 to find studies examining spinal sfSRS. Search parameters included the terms “single-fraction, spine, radiation SRS OR SBRT” Articles including multi-fractionated regimens only, reviewed sites outside of the spine, or did not report on clinical outcomes/toxicities were excluded. Results: 17 articles met initial inclusion criteria; 9 were added from references for a total of 26 articles comprising at least 2,699 patients (one study reported the number of tumors, not patients). Dose ranges for single-fraction SRS were 8-26 Gy. Commonly noted toxicities were fatigue, nausea/vomiting, and dermatitis which were no worse than moderate/minimal, not requiring invasive intervention. The overall rate of VCF was 16.2%, with an increased propensity at &gt;20 Gy. The proportion of reported segments requiring surgical intervention (operative stabilization, vertebroplasty/kyphoplasty) for VCF after single-fraction SRS was 20.2% (33/163). The rate of TE fistula at 25 Gy was 8.3%, with an overall rate (dose range = 10-28 Gy) of 1.3% with up to 12-years of follow-up. In patients receiving median dose of 24 Gy, the rate of severe esophagitis was 6.8%, myositis was 1.3% (at 1-year) and 8.3% (at 5-years). The rate of peripheral nervous system injury was 2.5% (at 18-26 Gy) and pain flare was 8% (at 16-24 Gy). The rate of ureteral and esophageal stricture was 1.9% each in patients receiving 12-24 Gy. Conclusions: VCF is the most commonly reported severe adverse events with single-fraction spine SRS, particularly for doses &gt; 20 Gy. 80% of VCFs can be successfully managed without invasive intervention. Other severe adverse events are rare – particularly for &lt; 20 Gy – but require post-SRS monitoring to expediently and efficiently intervene if necessary. These findings indicate that single-fraction spine SRS to &lt; 20 Gy is safe with minimal morbidity. Further study regarding the efficacy of such dosing is being evaluated in ongoing clinical trials.
Impact of social media messages on perceived risk and severity of adverse effects and regret of HPV vaccination: The moderating role of decision-making preference.
Authors: Jorge Villegas, Cheng-Chia (Brian) Chen, Min Jee Lee
Journal: Journal of Clinical Oncology (2023)

10543 Background: The HPV vaccine has proven to be a highly effective and safe public health intervention for reducing the risk of various types of cancer. Despite its efficacy and safety, misinformation and negative opinions about the vaccine on social media can lead to negative emotions such as regret among those who have received it. This study investigated the impact of different content of social media messages on perceived risk and severity of adverse effects and regret of HPV vaccination. Methods: An experiment was designed to expose participants to messages posted on social media that manipulated the number of Vaccine Adverse Effects and the appeal used (narrative vs. statistics). The study measured the effect of the message on decisional regret and also assessed preferred level of involvement with medical decision-making. The online study was implemented among college students enrolled in a Midwestern or a South Texas university. We used structural equation modeling (SEM) to systematically test the relationships between the variables of interest. Results: A total of 721 participants were exposed to the experimental materials and completed the questionnaire. The results of the SEM (with overall good fitness of RMSEA = 0.015, CMIN/df = 1.172) suggest that messages that contained more numeric information (standardized regression weights [Std Reg Wght = 0.161]) and more adverse effects of the HPV vaccine (Std Reg Wght = 0.076) led to a higher perception of the risk of vaccine adverse effects. The severity of adverse effects was significantly associated with the number of side effects in the message (Std Reg Wght = 0.147). This increase in perceived risk (Std Reg Wght = 0.182) and severity of side effects of the vaccine (Std Reg Wght = 0.163) seem to increase decisional regret. However, this relationship was moderated by individuals’ preferences for making their own medical decisions. Individuals with a higher preference to make their own health decisions were less likely to experience decisional regret (Std Reg Wght = -0.238). Conclusions: Messages on social media can exacerbate negative emotions and lead to hesitation in following future medical advice. Encouraging individuals to play a more active role in their medical decision-making appears to reduce this negative emotion and increase their confidence in health decisions.